To describe the natural history of ischemic digital ulcers (DU) in systemic sclerosis (SSc).
This single-center, retrospective, longitudinal study identified patients by demographic data, SSc history ...and type, Rodnan score, tobacco use, presence of autoantibodies, ongoing treatment, and DU history.
One hundred three patients were enrolled, 46 with DU history and 57 without; 2 with DU were excluded. The mean duration of followup from the first non-Raynaud SSc symptoms was 12.3 +/- 6.3 years in patients with DU history and 12.1 +/- 7.0 years in patients without. In 43% of cases, first DU occurred within 1 year following first non-Raynaud SSc symptoms, and within 5 years in 73% of cases. In a multivariate analysis, younger patients at occurrence of first non-Raynaud SSc symptoms (HR = 0.77 per each 5 years older, 95% CI 0.66-0.90) with higher Rodnan scores (HR = 1.21 per 5 points, 95% CI 1.05-1.47) experienced earlier DU occurrences, which were delayed by vasodilator therapy (HR = 0.17, 95% CI 0.09-0.32). Patients with shorter durations between first and second DU episodes, particularly with a second episode within 2 years of the first, experienced a higher yearly incidence of DU episodes (0.85 +/- 0.57 and 0.48 +/- 0.26, respectively, if less or more than 2 yrs; p = 0.04). Throughout the duration of followup, the incidence of finger amputation was 1.2% per patient-year in patients with DU history.
Patients who are young at first sign of SSc, with high Rodnan scores and without vasodilator therapy, are at high risk of developing DU. Development of DU typically occurred within 5 years of the first non-Raynaud clinical symptom of SSc in the majority of patients.
Background
Granulomatous disease (GD) will develop in a subset of patients with common variable immunodeficiency (CVID). Little is known about the efficacy of therapeutic agents used for treating ...this disorder.
Objective
To evaluate the efficacy of immunosuppressive drugs with the help of a set of clinical, biological and radiological criteria.
Method
Clinical and laboratory features of CVID patients were collected from the French DEFI cohort, a prospective study on adults with hypogammaglobulinemia. The medical charts of 55 patients (93 %) of the GD cohort were reviewed.
Results
Among 436 subjects with CVID, 59 patients (13.5 %) were diagnosed with GD. Of the 55 patients in whom medical charts were available, 32 patients received treatment for the granulomatous disease. Corticosteroids were the most frequently used drug. Complete response to treatment was infrequent. It was achieved with corticosteroids, cyclophosphamide, hydroxychloroquine, rituximab and methotrexate. Azathioprine, cyclosporine, mycophenolate mofetil, sirolimus, infliximab and thalidomide led to partial or absence of response. Complete and partial responses were observed in lymph nodes, lungs, liver, skin, bone marrow and central nervous system. Absent of response for gastrointestinal tract granulomas was noted in all cases of treatment attempt.
Conclusion
CVID patients with GD exhibit a particular biological phenotype. Treatment should be considered in any symptomatic patient or if there is evidence of organ dysfunction. Corticosteroids are the drug of choice in most instances but response to treatment is often unsatisfactory.
To evaluate the effect of iterative reconstruction on the depiction of systemic sclerosis-related interstitial lung disease (ILD) when the radiation dose is reduced by 60%.
This study was based on ...retrospective interpretation of prospectively acquired data over a 12-month period and approved by the institutional review board. The requirement to obtain informed consent was waived. Fifty-five chest computed tomographic (CT) examinations were performed in 38 women and 17 men (mean age, 55.8 years; range, 23-82 years) by using a dual-source CT unit with (a) both tubes set at similar energy (120 kVp) and (b) the total reference milliampere seconds (ie, 110 mAs) split up in a way that 40% was applied to tube A and 60% to tube B. Two series of images were generated simultaneously from the same dataset: (a) standard-dose images (generated from both tubes) reconstructed with filtered back projection (group 1, the reference standard) and (b) reduced-dose images (generated from tube A; 60% dose reduction) reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE) (group 2). In both groups, the analyzed parameters comprised the image noise and the visualization and conspicuity of CT features of ILD. Two readers independently analyzed images from both groups. Results were compared by using the Wilcoxon test for paired samples; the 95% confidence interval was calculated when appropriate.
The mean level of objective noise in group 2 was significantly lower than that in group 1 (22.02 HU vs 26.23 HU, respectively; P < .0001). The CT features of ILD in group 1 were always depicted in group 2, with subjective conspicuity scores (a) improved in group 2 for ground-glass opacity, reticulation, and bronchiectasis and/or bronchiolectasis and (b) identical in both groups for honeycombing. The interobserver agreement for their depiction was excellent in both groups (κ, 0.84-0.98).
Despite a 60% dose reduction, images reconstructed with SAFIRE allowed similar detection of systematic sclerosis-related ILD compared with the reference standard.
The aim of the study was to describe the evolution of mortality and cause-specific mortality over time in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN), ...granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).
Patients with SNV from the French Vasculitis Study Group registry were divided into 5 groups according to the date of diagnosis: <1980, 1980–1989, 1990–1999, 2000–2010, and ≥ 2010. The causes of death were classified as vasculitis, infection, cardiovascular, malignancy, miscellaneous, or unknown.
Among the 2217 patients included (PAN 16.1%, GPA 41.7%, EGPA 22.6%, MPA 19.6%), overall incidence of death was 2.26 per 100 person-years. The overall survival improved during each period considered. The 5-year survival rate increased from 72.2% (95% confidence interval CI 59.7–87.2) for patients diagnosed before 1980 to 94.5% (95% CI 90.4–98.8) after 2010 (p < 0.001). Periods of diagnosis, age, and male gender were independently associated with a poor survival with a non-significant difference between vasculitis. The incidence of mortality between the 1980s and after 2010 significantly decreased for vasculitis-related (p = 0.03) and cardiovascular-related deaths (p = 0.04). Incidence of death by infection remained stable between the 1980s and the 2000s but no death by infection occurred after 2010. The incidence of death by malignancy remained stable over time.
Overall survival of SNV patients has improved since the 1980s with the decrease of vasculitis- and cardiovascular-related deaths, but cancer-related mortality remained stable. These results highlight malignancy as the current target to improve the overall prognosis.
•Overall survival of SNV patients has dramatically improved since the 1980s.•Vasculitis-related mortality is nowadays rare reflecting the progress in the treatment of SNV.•Side effects of immunosuppressive drugs reflect the current target in SNV.
A germline and coding polymorphism (rs2230926) of TNFAIP3 (A20), a central gatekeeper of nuclear factor-kappa B (NF-kB) activation, was recently found associated with primary Sjögren's syndrome ...(pSS)-associated lymphoma in a French cohort. We aimed to replicate this association.
The rs2230926 polymorphism was genotyped in cases and controls of European ancestry from two independent cohorts from UK and France. Case control association tests were performed (Fisher's test) in the two cohorts, followed by a meta-analysis of the two cohorts.
The UK cohort included 308 controls and 590 patients with pSS including 31 with a history of lymphoma. The French cohort consisted of 448 controls and 589 patients with pSS including 47 with lymphoma. In both cohorts, the rs2230926 missense polymorphism was not associated with pSS. However, in the UK cohort, the rs2230926G variant was significantly associated with pSS-associated lymphoma (OR=2.74, 95% CI (1.07 to 7.03), p=0.0423, compared with patients with pSS without lymphoma, and OR=3.12, 95% CI (1.16 to 8.41), p=0.0314, compared with healthy controls) as observed in the French cohort. The meta-analysis of the two cohorts confirmed these results (OR=2.48, 95% CI (1.87 to 3.28) p=0.0037 and OR=2.60, 95% CI (1.91 to 3.53) p=0.0031, respectively).
This study confirms the role of A20 impairment in pSS-associated lymphoma. Subtle germline abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhance the risk of lymphoma.
TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever and/or elevated serum C-reactive protein, renal ...dysfunction, and organomegaly.
A 28-year-old woman with fever, weight gain of 13 kgs, lower extremity edema, hepatosplenomegaly, and multicentric peripheral lymphadenopathy was referred to our center. Laboratory investigations revealed anemia, thrombocytopenia, creatinine at 1.19 mg/dL and hypoalbuminemia at 33 g/L. Proteinuria was measured at 2 g/day including albuminuria at 1.5 g/day. Urinary sediment examination found leukocyturia at 44,000/mL and hematuria at 645,000/mL. Vascular endothelial growth factor (VEGF) level was elevated. A cervical lymph node biopsy found features consistent with the mixed histopathological subtype of iMCD. A renal biopsy revealed a membranoproliferative glomerulonephritis (MPGN) pattern. We initiated 3 days of methylprednisolone pulse-therapy at 1,000 mg per day, followed by prednisone 1 mg/kg/day and evolution was favorable.
19 iMCD patients with TAFRO syndrome had undergone a renal biopsy: 8 cases with author's diagnosis consistent with MPGN-like and 11 cases of thrombotic microangiopathy (TMA)-like glomerulopathy without fibrin thrombi in glomerular capillaries or arterioles and without typical biological signs. Clinical, biological, and outcome characteristics were similar between the cases described as having MPGN and TMA-like presentation. After a thorough review of histopathological descriptions for each case, MPGN lesions seems to be the consequences of chronic glomerular endothelial injury in persistent TMA. We suspect that VEGF and IL-6 play a key role in the physiopathology of the spectrum of renal involvement from TMA-like to MPGN observed in TAFRO syndrome.
We present a Caucasian iMCD patient with TAFRO syndrome with renal insufficiency secondary to MPGN, which might be secondary to a chronic TMA-like disease. We suspect that there is a continuum between TMA and MPGN lesions in TAFRO syndrome favored by VEGF and IL-6.
Objective
The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases involves health care providers (HCPs) from 8 European countries and 7 patients’ ...representatives of European Patient Advocacy Groups. The objective was to evaluate current practice and unmet needs for patient education (PE) in Europe.
Methods
A questionnaire was sent to HCP members asking about the PE practices and another, to enquire about their needs, was sent to patients’ associations in the different countries.
Results
The questionnaire was completed by 33 HCPs. Half had no specific staff members dedicated to PE. For HCPs with dedicated staff, 83.3% (n = 11) considered that care providers were insufficient to meet patients’ needs. Most of HCPs would like to see the practice of PE standardized. Sixty eight percent (n = 1093) of patients suffering from connective tissue diseases completed the questionnaire had never heard about PE. Most of them were interested in taking part in a PE program.
Discussion
Our survey revealed a strong interest in PE among patients and HCP and heterogeneity of practice. PE appeared important for both HCPs and patients. An online course for medical students in Europe will be developed in partnership with EULAR to respond to these unmet needs.
Abstract
Background
Interstitial lung disease is a common complication of systemic sclerosis (SSc-ILD), and it remains difficult to accurately predict its course. Progressing ILD could be more ...metabolically active, suggesting that the
18
F-FDG tracer could be a tool in the managing of SSc-ILD.
Methods
In our center, SSc patients and controls (non-Hodgkin lymphoma cured after first-line regimen) who had received a PET/CT were screened retrospectively. The FDG uptake (visual intensity, pattern, SUV
max
) was systematically recorded in > 30 regions of interest (ROIs) linked to SSc in a blind reviewing by 2 independent nuclear medicine physicians using a standardized form.
Results
Among the 545 SSc patients followed up in our center, 36, including 22 SSc-ILDs, had a PET/CT, whose indication was cancer screening in most cases. The mean ± SD age was 57.9 ± 13.0 years with 20/36 females. Fourteen patients had a disease duration of less than 2 years. A third had anti-centromere antibodies and 27.8% had anti-topoisomerase antibodies. Pulmonary FDG uptakes were higher in SSc patients than in controls (
n
= 89), especially in those with ILD compared with those without ILD. Pulmonary FDG uptakes were positively correlated with the ILD severity (fibrosis extent, %FVC, and %D
LCO
). No significant difference was found in the FDG uptakes from extrathoracic ROIs. Progressing SSc-ILDs within the 2 years after PET/CT (
n
= 9) had significant higher pulmonary FDG uptakes at baseline than stable SSc-ILDs (
n
= 13).
Conclusion
PET/CT could be a useful tool in the assessment of the severity and the prediction of pulmonary function outcome of SSc-ILD.
The risk of early death is particularly high in patients over the age of 65 presenting with antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis. We hypothesized that by combining ...disease severity markers, a comorbidity index and serious adverse event reports, we would be able to identify early predictors of one-year mortality in this population.
We performed a multicentre, retrospective study in the nephrology and internal medicine departments of six tertiary hospitals in northern France. A total of 149 patients (median interquartile range (IQR) age: 72.7 68.5-76.8 years) presenting with ANCA-associated vasculitis and renal involvement were included between January 2002 and June 2015. The primary endpoint was the one-year mortality rate.
Renal function was severely impaired at presentation (median IQR peak serum creatinine (SCr): 337 211-522 μmol/l), and 45 patients required dialysis. The Five-Factor Score (FFS, scored as + 1 point for each poor prognostic factor (age > 65 years, cardiac symptoms, gastrointestinal involvement, SCr ≥150 μmol/L, and the absence of ear, nose, and throat involvement)) was ≥3 in 120 cases. The one-year mortality rate was 19.5%. Most of the deaths occurred before month 6, and most of these were related to severe infections. In a univariate analysis, age, a high comorbidity index, a performance status of 3 or 4, a lack of co-trimoxazole prophylaxis, early severe infection, and disease activity parameters (such as the albumin level, haemoglobin level, peak SCr level, dialysis status, and high FFS) were significantly associated with one-year mortality. In a multivariable analysis, the best predictors were a high FFS (relative risk (RR) 95% confidence interval (CI) = 2.57 1.30-5.09; p = 0.006) and the occurrence of a severe infection during the first month (RR 95%CI = 2.74 1.27-5.92; p = 0.01).
When considering various disease severity markers in over-65 patients with ANCA-associated renal vasculitis, we found that an early, severe infection (which occurred in about a quarter of the patients) is a strong predictor of one-year mortality. A reduction in immunosuppression, the early detection of infections, and co-trimoxazole prophylaxis might help to reduce mortality in this population.
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